In this project we will develop a vaccine approach using dendritic cells for the treatment of malignant B cell lymphoma. We will build on our prior experience with dendritic cells in which immunoglobulin idiotype from each patient's tumor was used as the antigen and in which safety, immune responses and anti-tumor effects were documented. We will now develop a similar approach in which whole tumor cells will be used as the antigen source and dendritic cells, or exosomes derived from such cells, will be used as the delivery vehicle. This will allow vaccination against the entire constellation of tumor antigens expressed by the lymphoma cell, including immunoglobulin idiotype. We anticipate that such an approach would elicit a broader and more potent anti-tumor immune response. We will begin with animal models and in vitro human systems, in which we will determine the optimum methods for induction of appropriate immune responses. In the animal models the goal will be to induce protection against the growth of the lymphoma. In the human system the goal will be to induce autologous cytotoxic T cell responses against patients' own tumors. The most effective method will then be employed in a human clinical trial in patients with lymphoma who have failed conventional therapy. Through the use of dendritic cells or exosomes expressing a wide range of autologous tumor epitopes, we hope to develop a highly effective and broadly applicable vaccine for lymphoma.